Highlights of the Annual Scientific Meeting of NAASO, The Obesity Society

October 20-24, 2006; Boston, Massachusetts

Heather K. Stein, MD, MPH

Disclosures

January 05, 2007

In This Article

Pharmacotherapy

The preconference session reviewed pharmacotherapy for obesity. Barbara E. Corkey, PhD, Boston University School of Medicine, Boston, Massachusetts, discussed peripheral targets for the treatment of obesity, including the gastrointestinal tract and adipose tissue.[2] She emphasized that research can no longer focus on single proteins, but must now examine multiple protein targets.

Alain Baron, MD, Amylin Pharmaceuticals, Inc, San Diego, California, discussed pramlintide, a diabetes medication that also has been shown to cause weight loss, even in patients taking insulin.[3] He presented animal data showing a synergistic effect on weight loss when pramlintide was administered with leptin, and even greater weight loss when pramlintide was administered with leptin and peptide YY. These results in rats suggest that a combination of pharmacologic agents might approach the significant weight loss seen after bariatric surgery. Further studies need to be performed in human subjects to determine whether the effects of surgery could be replicated with a combination of pharmacologic agents.

The process of drug development and approval takes, on average, approximately 9 years and costs, on average, $1.7 billion. These expenditures include the costs of studies examining the efficacy and safety of the medication. Julie Golden, MD, US Food and Drug Administration (FDA), reviewed the complex process of drug approval.[4] George Bray, MD, Pennington Biomedical Research Center, Baton Rouge, Louisiana, reviewed the history of pharmacotherapy, with a focus on medications that have been removed from the market due to safety concerns.[5] Louis Aronne, MD, Weill Cornell Medical College, New York, NY, emphasized the need for drug safety in clinical practice, using the experience with fen-phen (the combination of fenfluramine and phentermine) as an example.[6] Mark McCamish, MD, PhD, Amgen, Inc, Thousand Oaks, California, discussed the topic of pharmacogenomics and whether there is a genetic contribution to patients' responses to a medication either in its therapeutic effect or risk for adverse events.[7]

The idea of combination therapy and the emphasis on safety were also reflected in other presentations, including:

  • A study by Greenway and colleagues[8] on the effect of combination therapy with bupropion and zonisamide for the treatment of obesity, which found that at 16 weeks patients on the combination of both medications had a mean weight loss of 8.3%, whereas those on bupropion, zonisamide, or placebo alone lost 3.7%, 5.7%, and 0.7%, respectively. At 48 weeks, patients on 200 mg and 400 mg of zonisamide experienced a mean weight loss of 3.1% and 9.3%, respectively, whereas those on bupropion and either 200 mg or 400 mg of zonisamide experienced a mean weight loss of 8.4% and 12%, respectively.

  • A study by Gadde and colleagues[9] on the combination of phentermine and topiramate for the treatment of obesity, which showed that patients on both medications lost an average of 11.4 kg over 24 weeks, whereas patients on topiramate, phentermine, or placebo lost 6.6, 5.3, and 2.2 kg, respectively.

  • A study by Qu and colleagues[10] examining the effect of exenatide vs insulin therapy in patients with type 2 diabetes who were on a sulfonylurea and metformin. The 26-week study revealed that compared with the addition of insulin glargine, the addition of exenatide resulted in equivalent improvement in glycemic control, with a decrease in glycated hemoglobin (A1C) of 1.1% in both groups. However, 22.1% of patients lost ≥ 5% body weight and 4.3% lost ≥ 10% body weight in the exenatide-treated group, whereas only 2.6% of patients lost ≥ 5% body weight and 0.4% of patients lost ≥ 10% body weight in the insulin-treated group.

These studies are examples of the potential success of combination therapies to treat obesity. These are only preliminary trials, however, and further studies on the efficacy, dosing, and safety of combination therapies are needed before they can be put into regular clinical practice. The studies on exenatide demonstrate how progress in drug development, even in other therapeutic areas, can reveal novel targets that enhance the understanding of the physiology and treatment of obesity.

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